Pigmentary Disorders: A Comprehensive Compendium Rashmi Sarkar, Koushik Lahiri, Manas Chatterjee
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History and Evolution of Pigmentary Disorders in Human1

Amiya Kumar Mukhopadhyay
“Those about to study Medicine, and the younger Physicians, Should light their torches at the fires of the Ancients”
— Rokitansky

Key Features

  • Historically the idea and concentration of pigmentary disorders mostly revolved around white-spot (or patch) diseases. These white-spot diseases could range from vitiligo to leprosy, psoriasis and many other similar or dissimilar disorders of modern phraseology.
  • Almost all major ancient and religious texts throughout the world mention about skin diseases, of which leprosy and/or vitiligo had gained the most importance. Rituals regarding “clean” and “unclean” from disease were prevalent in all major communities.
  • Most of the pigmentary disorders of present day have been described in last 200–300 years after the discovery of pigment cell and its biology.
 
INTRODUCTION
The study of the history is an integral part of the process of going into the deeper and broader aspect of any subject as far as the evolution, present status and the foretelling (depending on the past experience and sense of logic) of that subject is concerned. This is true in the study of pigmentary disorders too.
As the early ancestors of the human race moved out of Africa about 100,000 years ago, the diversity of skin color appeared due to various reasons. This lead to the idea of “normal” color of people living in a common condition, and any variation beyond a certain limit was considered abnormal giving rise to the entities of various pigmentary disorders. The impact of pigmentary disorders on the social system was so prominent that it could be seen in almost all the major religious and ancient texts across the globe. The stigma and the morbidity of these disorders had prompted the physicians and health scientists from the early days to search for the root and remedy of these problems.
The pigmentary disorders, for the purpose of discussion from the historical point of view, may be broadly grouped into:
  • Disorders of de- and/or hypopigmentation
  • Disorders of hyperpigmentation
  • Disorders of aberrant pigmentations
  • Man-made pigmentary disorders, e.g. tattoos.
Also the topics will be discussed in two shades of time frame:
  1. From early historical period till 18–19th century AD.
  2. From 18–19th century AD (the beginning of modern dermatology) till present time.
 
Disorders of De- and/or Hypopigmentation in Ancient Literatures of the East
Any partial or complete loss of skin color has attracted attention of the community from time immemorial. From the ancient days till last 200–300 years back any hypopigmented (or even scaly!) diseases of the skin were lumped into a common entity: white spot or vitiligo. Of the various de-/hypopigmentary diseases leukoderma (vitiligo) received the lion's share of the dialogue and attention from the ancient time. The exact period of beginning of the history of vitiligo is really difficult due to the imprecision of translation of archaic literatures in the light of modern views and also because of the conceptual and nosological confusions that existed regarding the exact and scientifically defined nature of the disease.2
A brief pigmentary disorder timeline
2200 BC:
First known description of vitiligo
1550 BC:
Ebers papyrus describes pigmentary disorders among other skin diseases
1500 BC:
Atharva Veda mentions about white-spot disease and its remedy
1200 BC:
Shinto prayer book Makato minoharai mentions shira bito—a disorder of hypo-/depigmentation
800–500 BC:
Indian Ayurvedic texts like CS and SS describes about the etiology, classification, management and prognosis of different pigmentary disorders
449 BC:
Greek scholar Herodotus wrote about white-skin disease
250 BC:
Translation of Hebrew Bible to Greek took place. Controversy regarding the exact meaning of zara'at begins
25 BC–50 AD:
Period of Celsus. First to introduce the term vitiligo
700–800 AD:
Aṣṭanga hṛdaya of Vagbhatt mentions a condition called jatumani—a reddish birth mark (portwine stain or other vascular nevi)
980–1037 AD:
Period of Arabic physician Avicenna. Describes about various pigmentary disorders in his al Qanun.
17th century AD:
Malpighi publishes first scientific paper on skin color
18th century AD:
Hunter dissected pigment layer from the skin
1917 AD:
Bruno Bloch mentions dopa–reaction to stain melanin
1948 AD:
Mason classified melanin
1988 AD:
Fitzpatrick classified the skin into six sun-reactive types.
With the advent of modern laboratory techniques various disease entities with the features of diminution or loss of color is emerging in the scientific literature in recent time. In this situation the condition that in the following section will be viewed upon as vitiligo, may be any disease that might or might not be the vitiligo of modern day definition, even in some cases it could be leprosy, psoriasis and other diseases of patchy and discolored configuration.
The first historical description of vitiligo is found during the period of Ausooryan (c. 2200 BC) as has been discussed in Tareekh-i-tibb-i-iran.1,2 In the winter of 1872, the German Egyptologist George Ebers purchased a 110-page, about 20 meter long scroll at Luxor, which contained an amazing scenario of medicine of the ancient civilization of Egypt. Though these papyri were dated to a period of c. 1550 BC, but the subjects were a compilation of practice that were prevailing since last few hundred to thousands of years.3 Among the various skin diseases and tumors mentioned, the interesting description of a skin condition could be that of vitiligo.4
Vedas are the ancient scriptures of the Indo-Iranian Aryans whose antiquity is yet to be ascertained, though most authorities believed the period of compilation to be 1500–1000 BC or much earlier.5 Among the four Vedas the Atharva Veda is more concerned with diseases than the others. The mention of a condition kilāsa most probably describes leukoderma (vitiligo) which is very much apparent in the following hymn:
“naktaṃ jatsyouṣadhe rame kṛṣne asikni ca
idaṃ rajani rajaya kilāsam palitaṃ ca ya't”
—Atharva Veda I.23.1.
“Night-born art thou, O herb, O dark, black (and) dusky one; O colorer, do thou color this hypopigmented (?) spot and which is pale.”
The two charms I.23 and I.24 of the Atharva Veda specifically deal with the white spots and their remedies. In the hymns I.24.3–4 prayers have been offered to the herb for the restitution of the normal hue on the affected skin.6 The use of some black seeds along with other herbs like Bhringaraja, Indravaruni and turmeric is also mentioned as a treatment.7
Avesta is another sacred scripture of the Indo-Iranian Aryans. It also mentioned about vitiligo.8,9
In the later Vedic period, particularly during the period of early Buddhism the prevalence of leukoderma is evident in major text like Mahavagga (1.39, 1.76.1) of the Vinay Pitaka (624–544 BC).10
In the process of evolution of medical system that started from the early Vedic era or even earlier, Āyurveda—the science of life, appeared as a special subject dealing exclusively with disease and remedies. The pigmentary disorders were dealt in detail in major texts like Caraka Samhitā (CS), Suśruta Samhitā (SS), Bhela Samhitā (BS) and others.
In the CS (c. 800–600 BC), the word svitra stands for some hypo-/depigmentation and have been further subdivided in to three varieties: (1) dārūna, (2) arūna and (3) kilāsa and it also mentioned that when the perturbed dosa (humor) affects the meda (fatty tissue), the color of the disease becomes white. The white spots may merge with one another and leukotrichia and extensive involvement of skin was considered bad prognostic signs and also considered difficult to treat (CS Cikitsā Sthānam 7).11
In SS (c. 500 BC), the word kilāsa was used for leukoderma and it had been differentiated from leprosy by the fact that 3kilāsa was never a discharging condition whereas, kuṣṭha (leprosy) could be a discharging disease. This treatise also specifically mentioned that white spots affecting palms, soles, anal orifice and those developed as a result of burn is difficult to cure:
“…tesu sambandhamandalamante jātaṃ raktaroma ca sādhyamagnidagdhaṃca”
—(SS Nidānasthānam 5:12)12
The ancient Hindu law book Manu-smriti (c. 200 BC) bore references of leukoderma (svitra) and said that a stealer of clothes would suffer from the disease as a result of his misdeed in the earlier live (XI.51). It forbade marriage with a subject or the family affected with svitra (III.7) and also prescribed that in a religious and social occasion even a Brahmin affected with svitra should not be invited (III.161).13
The Bower manuscript (compilation c. 450 AD) in the leaf I verse 5–9 also mentions vajraka tailam—a medicated application for the treatment of svitra.14 the ancient Saṃskṛt book of lexicon Amarakoṣa (AD 600) described svitra as leukoderma.15
Other famous texts of ancient Saṃskṛt literature like Aṣṭāṅga-hṛdaya-Saṃhitā (c. 7–8th century AD), Mādhava-Nidān (c. AD 700), Cakradattā (c. 11th century AD), SŚārandhar Saṃhitā (c.13th century AD) have elaborately mentioned about the white spot diseases and its remedies.16–19
The mention and description of vitiligo is prevalent in the old literatures of the other Eastern nations like China, Japan and Korea. In Makatominoharai, a Shinto prayer book (c. 1200 BC) the word Shira-bito stands for leukoderma.20,20a The first description of vitiligo and other hypopigmentary conditions in Chinese literature is found during Sui dynasty (618–626 AD). The classification of vitiligo into localized and generalized was done during the Sung dynasty (960–1279 AD). The early description of hypopigmentary disorder is found in Dongey Bogam—an early 17th century Korean medical book. The 18th century paintings showing the nobles afflicted with vitiligo have been published in the literature.21
zoom view
Figs 1A and B: Vitiligo and chloasma.[Source: Jerome Kingsbury's Portfolio of Dermachrome (1921)]
In the Siddha system—an ancient Tamil medical system (c. 400 AD or even earlier) there is mention of white skin diseases and its remedy.22
In the holy book of Islam Al'Quor'ān some verses like verse 49 of Al-'Imran (Chapter 3) and verse 110 of Al-ma'idah (Chapter 5) there is mention about a disease resembling leukoderma.23
In the famous medical text of the Greco-Arabic medicine al-Qanun fi-al-tibb (11th century AD), Alī al-Husayn ibn ‘abd Allāh ibn Sinā (980–1037), popularly known as Avicenna in the Western world has given description of leukoderma (Bahaq and Baras).24
 
Disorders of De- and/or Hypopigmentation in Ancient Literatures of the Western World
The analyses of medical system of the Western world showed that the idea about the hypopigmentary disorders was developing since the early period of the history. The famous Greek scholars Herodotus (484–425 BC) in the First Book “Clio” composed in 449 BC wrote that a native with white sickness should not be allowed to enter the city and a foreigner afflicted with this be driven away from the country.25 Other great scholars like Hippocrates (460–370 BC) and Aristotle (384–324 BC) also mentioned about this disease in their literatures.26,27
The Illustrious Latin medical author Aulus Cornelius Celsus (25 BC–50 AD) of Rome first used the term vitiligo and wrote about it in the Chapter 28 of his fifth book “De Medicina” and divided the entity into: Alphos, Melas and Leuce. Of these Leuce probably represented vitiligo.28
The most discussed topic about leprosy-vitiligo is centered on the Biblical reference about the disease. The mention of white spot(?leukoderma, ?leprosy) can be found in Exodus 4:6, Leviticus 13,14,21, numbers 5:2,12:10, Deuteronomy 24:4S II Samuel 3:29,II Kings 5:27II Chronicles 26–19:23 of the Old Testament and Matthew 8:2–3,10:8,11:5, Mark 1:40,14:3, Luke 4:27,17:12–19 of the New Testament.29 The Biblical controversy of leprosy-vitiligo started in 250 BC during the period of Ptolemy II, the Septuagint translation of Hebrew Bible into Greek took place. It translated the Hebrew word Zara'at (Leviticus 13) to lepra. Most authorities believe that the entity was not leprosy but some other skin disease(s)—one possibility could be vitiligo.25,30
The controversy went on for centuries and it has been opined that some of the “leper knights” of the order of St. Lazarus fighting the Crusade in 13th century were not actually lepers but were suffering from vitiligo.31
Hieronymus Mercurialis (1530–1606) in his “De Morbis Cutaneis et Omnibus Corporis Humani excrementis Tractaus”—the first ever book on skin diseases written in 4Latin in 1572 mentioned about different varieties of white patches and told about their remedies.32
These confusion and debate continued till the beginning of modern day dermatology when the classification of diseases and contributions from great authorities like Plenck, Willan, Batemen, Alibert, Hebra and others lead to the clearing of the cloud. This will be discussed in other section of this chapter.
 
Disorders of Hyperpigmentation
The issue of hyperpigmentation has, surprisingly been attracted much less attention of the ancient medical men both in the East as well as West. As some conditions like melasma, birth marks (e.g. melanocytic nevi), postinflammatory hyperpigmentation are quite prevalent in all societies, so these conditions were probably considered normal and hence did not attract much attention.
There is mention of various kṣhetriya (hereditary and/or congenital) disorders in the Atharva Veda (V.II.8.1–8, II.10.1–8, etc.). Whether some of them were associated with any pigmentary manifestation is not very clear. The very clear description of hyperpigmentary condition is available in major Āyurvedic texts like Caraka Saṃhita, Suśruta Saṃhita, Aṣṭangahṛdaya, Mādhavanidān and others.
Melasma has been described as vyanga in Caraka Saṃhita, Suśruta Saṃhita, Aṣṭanga hṛdaya, Śarangdhara and others.33–37
The astute physicians of the ancient India also noted the darkening of the lips and areolae of breasts from the third month of pregnancy (Caraka Saṃhita, Śarīrasthānam 14).38
The change of skin color and its prognostic importance in various diseases have also been described in the Indriyasthānam section of the Caraka Saṃhita. It has been said in the same section of the book that sudden appearance of melanocytic nevi (? pigmented seborrheic keratoses), melasma should considered as ominous sign.39
In the Greco-Arabic medicine similar observations have been made. Various sections of the Avicenna's al-Qanun fi-al-tibb (11th century AD) describes about various changes in skin color and their significance.40
 
Disorders of Aberrant Pigmentations
Apart from the classical leukoderma or vitiligo like pigmentary disorders, the various aberrations of the common normal skin color have received attention from the ancient time. Among them birth marks, moles and nevi, change of color in diseases (if we consider the change in skin color in a broader sense of pigmentary anomaly) and many other conditions were described in different literatures.
The Book I of the Atharva Veda mentions a condition called harimān and its remedy in verses 22.1–4 which stands for the yellowness of the body or jaundice in modern sense.41 Similar mention is also found in the Buddhist text of Mahavagga where a drink made of cow's urine and yellow myrobalan was used as treatment (Mahavagga 6.14.6).42
zoom view
Fig. 2: Vitiligo or leukoderma.[Source: Norman Walker's An Introducti on to Dermatology (1904)]
The later Vedic literatures like treatises of Caraka, Suśruta, Vagbhatt and others also enumerated different pigmentary changes. In CS the word halīmaka probably stands for biliary jaundice in which the greenish or blackish discoloration of the body were noted along with other systemic symptoms (Cikitsāsthānam 16:124–137). Hyperpigmentation of the lips and areola of the breast haven mentioned in raktagulama (molar pregnancy) (CS Nidānasthānam.3).43 The SS also described change of color in conditions like burn injury (Sūtrasthānam 12.13). It mentioned about tialakālaka (melanocytic nevi) and nyaccha (nevi and other birth marks that arise de novo. (SS. Nidānasthānam 13.35-36).44 In another famous text, Āṣṭānghṛdaya of Vagbhata mentions about melasma, nevi and birthmarks. The mention of a condition named jatumani, a reddish birthmark which was probably port wine stain or some other vascular nevi is interesting. (Uttarasthāna XXXI: 24–26).45
A number of diseases like Addison's disease, Fanconi's anemia, incontinentia pigmenti and many others are associated with pigmentary changes. Some nevi like Mongolian spots, nevus of Ota, nevos of Ito, Hori's nevus, and café au lait macules, etc. are responsible for pigmentary changes. The story of evolution of these conditions are interesting topic of the medical history, but could not discussed due to the want of space.
 
Man-made Pigmentary Disorders
The pigmentary changes of skin are not always an unwanted entity. Man from the early days of its history started performing tattoos for magical, religious, social, practical and medical reason apart from decorative. Sometimes it act as a totem, sometimes it was believed to protect the man from the demonic influences of harmful invisible satanic forces, but whatever be the reason the art is still in vogue. It has sometimes been used to hide the blemishes of different diseases. The interested reader may consult treatises and articles dealing in detail about the subject.46–505
The use of different drugs and chemicals like arsenic, clofazimine, chloroquine, amiodarone, etc. and misuses and side effects of some others like hydroquinone, topical potent and superpotent corticosteroids and many others may give rise to aberrant pigmentation causing some distinct disorders like exogenous ochronosis, Riehl's melanosis, poikiloderma of Civatte and others.
 
HISTORY AND EVOLUTION OF PIGMENTARY DISORDERS IN MODERN DERMATOLOGY
The medicine related to skin that used to be practiced as a part of surgery and general medicine gradually took the shape of a well-defined specialty during the last quarter of the 18th century.51 The science and art of skin diseases were not in a systematized state till then, but now got classified by Plenck, Willan, Alibert and others.52 But the history of pigmentary disorders was witnessing a major change in concept even before that. The first publication of scientific study of the skin color came from Malpighi in 17th century.53 In the following century John Hunter (1728–1793) dissected the pigment layer from the skin.54 The famous 18th century German philosopher Kant (1724–1804) believed that the excessive amount of a substance—phlogiston is the cause of dark coloration of the skin.55 The first evidence of the occurrence of pigment cell in the human dermis came from Baelz in1885.56 Bruno Bloch in 1917 described the dopa reaction for the identification of melanoblasts. In 1934 Du-Shane first showed that melanoblasts of the axonal system originated in the neural crest and Mason in 1948 classified the melanin into animal, plant and synthetic forms.53 These whole development lead to the revolution of pigmentary cell biology, diseases associated with it and their remedial methodologies. One after another diseases with pigmentary disorders were described. The research was not confined to the mere variation of colors but the spectrum included the malignant conditions pertaining to pigment and other cells too.57,58 The treatment protocol that started with the incantations, charms, amulets of the magico or empirico-magical system in the hands of the shamans now entered the most sophisticated laboratories of the pigment cell biologists and photobiologists.59

Notes on Transliteration

ā,ī,ū are longer forms of a,i,u
ṛ is pronounced as ri
c is pronounced as ch in chit
ṭ, ṇ are pronounced with retroflexion of the tip of the tongue towards the back of the palate
s is pronounced as sa in say
ṣ is as in shun
ś is pronounced as sh in shall
ṃ is called anusvāra that nasalize the preceding vowel.
 
CONCLUSION
The disorders of cutaneous pigmentation remained one of the interesting, but enigmatic issues since the very early days of human civilization. Even during the mid-18th century of the present Christian era the confusion was prevailing in the medical world about these disorders. A fascinating (!!)definition of vitiligo may be an amazing example in this regard:60
“Vitiligo (vitium) a kind of leprosy or cutaneous eruption consisting of spots, sometimes black, sometimes white, called morphea, alphus, melas, leuce; also in general a cutaneous eruption. Celsus & Pliny”. (Lexicon of the Latin language of Facciolati & Forcellini, edited by FP Leverett, Boston; Wilkins & Carter and Little & Brown, 1841).
However, strange this definition appears, the reality is: none of us can guarantee cure of most of the pigmentary disorders with the presently available armamentarium of therapeutics. But this statement will not appear as gloomy as it sounds and the rest part of this compendium will show that the ongoing researches would bring hope and relief for the sufferers and healers alike in coming days.
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